Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001837022 | SCV001949978 | benign | Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes | 2022-02-11 | reviewed by expert panel | curation | This NM_004958.4(MTOR): c.3117+34G>A (p.=) variant is a synonymous (silent) variant that occurs at a nucleotide that is not conserved according to a PhyloP <0.1 (BP7). The results from in silico splicing predictors MaxEntScan, spliceAI and varSEAK support that this variant does not affect splicing (BP4). The highest population minor allele frequency in gnomAD v2.1.1 is 0.004847 in the South Asian population, which is higher than the ClinGen BMEP threshold ([>=0.00185]) for BA1, and therefore meets this criterion (BA1). This variant was identified the homozygous state in >3 individuals within control databases (BS2). In summary, this variant meets the criteria to be classified as Benign for mosaic autosomal dominant overgrowth with or without cerebral malformations due to abnormalities in MTOR-pathway genes based on the ACMG/AMP criteria applied, as specified by the ClinGen Brain Malformations Expert Panel: BA1, BP4, BP7, BS2 ; -14 points (VCEP specifications version 1; Approved: 1/31/2021) |
Gene |
RCV001690116 | SCV001910488 | benign | not provided | 2020-04-13 | criteria provided, single submitter | clinical testing |